CCRC: A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Raltegravir Therapy

This study has been completed.
Sponsor:
Information provided by:
University of California, Davis
ClinicalTrials.gov Identifier:
NCT00661960
First received: April 16, 2008
Last updated: August 2, 2011
Last verified: August 2011
  Purpose

This research is being done to study how the immune system in the small intestine improves after taking antiretroviral (anti-HIV) medications. The main purpose is to measure the increase in the numbers of immune cells in the intestine to see if one type of HIV medication gives different results than other types of HIV medications.


Condition Intervention
HIV Infections
AIDS
Procedure: Upper Endoscopy and biopsies
Drug: raltegravir
Drug: efavirenz

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CCRC: A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Raltegravir Therapy

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • To correlate the increase in frequency of CD3+/CD4+ cells per cubic millimeter at the effector sites in the duodenal tissues obtained from volunteers to the antiretroviral therapy regimen over time. [ Time Frame: nine months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To measure the trough plasma and tissue drug levels in volunteers at the time of the upper endoscopy [ Time Frame: nine months ] [ Designated as safety issue: No ]
  • To correlate the level of HIV RNA per gram of duodenal tissue versus plasma HIV load and drug regimen received [ Time Frame: nine months ] [ Designated as safety issue: No ]
  • To measure the change in GALT CD4+ and CD8+T-cell subpopulations (naive versus memory) in volunteers receiving raltegravir versus NNRTI [ Time Frame: nine months ] [ Designated as safety issue: No ]
  • To assess GALT immune function and activation in volunteers receiving raltegravir versus NNRTI [ Time Frame: nine months ] [ Designated as safety issue: No ]
  • To explore whether the treatment regimen correlates with the changes in CD3+/CD4+ T-cell numbers [ Time Frame: nine months ] [ Designated as safety issue: No ]
  • To compare the level of immune reconstitution with respect to absolute numbers of CD4+ T-cells, the relative proportion of T-cell subpopulations in the tissue, and immune activation to a cohort of normal controls [ Time Frame: nine months ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: March 2008
Study Completion Date: March 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 1
HIV Negative volunteers
Procedure: Upper Endoscopy and biopsies
5 HIV-Negative volunteers will only undergo this single procedure - A gastroenterologist (specialist in intestinal disease) will pass a flexible endoscope tube connected to a video camera, into the stomach and small intestine, will examine these areas, and will biopsy (take small pieces of tissue--about the size of a grain of rice) these areas.
Active Comparator: 2
HIV-Positive volunteers taking raltegravir in combination with two other nucleoside reverse transcriptase inhibitors (NRTI) medications
Drug: raltegravir
400mg tablet twice daily by mouth for nine months
Other Name: Isentress
Active Comparator: 3
HIV-Positive volunteers taking efavirenz or any other non-nucleoside reverse transcriptase inhibitors (NNRTI) in combination with two other nucleoside reverse transcriptase inhibitor (NRTI) medications
Drug: efavirenz
600mg capsule once daily by mouth without regard to food
Other Name: Sustiva

Detailed Description:

While the world-wide AIDS epidemic continues to impact millions of individuals, effective anti-HIV medications have substantially reduced morbidity and mortality for those patients able to adhere to combination regimens. Despite improved survival, durable virologic suppression, and increases in peripheral CD4+T-cell counts in patients receiving potent antiretroviral therapy (ART), immune reconstitution remains incomplete as measured by a number of additional surrogate markers. Perhaps critically important among areas of apparent incomplete immune recovery is the gastrointestinal-associated lymphoid tissue (GALT), where CD4+T-cells repopulate very slowly, if at all. Raltegravir is a new ART agent from a novel class of HIV inhibitors, integrase inhibitors, that results in rapid suppression of HIV and recovery of peripheral CD4+T-cells. This project proposes to examine whether volunteers receiving raltegravir recover GALT immune cells more completely than those taking comparator ART.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • willing to sign consent form
  • no known GI pathology
  • no anticipated antiretroviral therapy adjustments or changes
  • males & females between the ages of 18 & 50 years
  • no active opportunistic infections (OI) or therapy for OI within 30 days of entry
  • can be on secondary prophylaxis with a history of AIDS defining illness
  • per standard of care requirements, all females of child-bearing potential must agree to use barrier methods to prevent pregnancy or be abstinent from activity while on study

Exclusion Criteria:

  • abnormal coagulation parameters (PT > or equal to 1.2 ULN)
  • thrombocytopenia (platelet count < 50,000 within 6 weeks)
  • contra-indications to upper endoscopy or conscious sedation
  • anemia (> or equal to grade 1)
  • aspirin, ibuprofen, warfarin or other agents that interfere with the coagulation cascade are prohibited within 1 week of endoscopy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00661960

Locations
United States, California
CARES Clinic
Sacramento, California, United States, 95814
UC Davis Medical Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Investigators
Principal Investigator: David M. Asmuth, M.D. University of California, Davis
  More Information

No publications provided by University of California, Davis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: David M. Asmuth, M.D. / Principal Investigator, University of California, Davis
ClinicalTrials.gov Identifier: NCT00661960     History of Changes
Other Study ID Numbers: 200715792
Study First Received: April 16, 2008
Last Updated: August 2, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Davis:
HIV Positive
AIDS
Antiretroviral Therapy
Gastrointestinal-Associated Lymphoid Tissue
Immune Reconstitution
treatment experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Reverse Transcriptase Inhibitors
Efavirenz
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 15, 2014